Abstract
Latex allergy has become increasingly common over the
last decade, largely as a result of the introduction of “universal
precautions” to prevent virus transmission. Type I immediate
hypersensitivity reactions, due to specific immunoglobulin
E (sIgE) directed against natural proteins found in rubber,
cause symptoms such as urticaria, rhino-conjunctivitis, asthma
and, most seriously, anaphylaxis. Type IV delayed hypersensitivity
reactions, due to T cells sensitised to the chemicals added
to rubber during manufacturing, cause allergic contact dermatitis.
Individuals who have repeated exposure to latex, particularly
mucosal exposure, are at increased risk of sensitisation.
Thus health care workers and patients with meningo-myelocele
(“spina bifida”) or congenital urological abnormalities are
especially likely to become sensitised. SIgE to natural latex
proteins may cross-react with proteins found in various foods.
Diagnosis of latex allergy is by clinical history and detection
of sIgE in vivo (skin prick testing [SPT]) or in vitro for
Type I hypersensitivity, or detection of sensitised T cells
by patch testing for Type IV hypersensitivity. Preventative
measures consist of avoidance of sensitisation in high-risk
groups and avoidance of exposure for patients who are already
sensitised. Specific safety measures should be discussed with
patients who have established Type I hypersensitivity.
Keywords
latex allergy, atopy, type I hypersensitivity, type IV
hypersensitivity, anaphylaxis, patch testing
What is Latex?
Latex is a milky sap, which is the cytoplasm of specialised
plant cells called lactifers, that form a network within the
plant and help to seal damaged areas. It consists of a complex
emulsion of droplets of natural rubber (cis-1, 4-polyisoprene)
and a hydrophilic mixture of proteins, resins, tannins, starches
and oils. More than 2,000 different plant species produce
latex, but almost all of the latex used for manufacturing
rubber goods comes from the commercial rubber tree Hevea
brasiliensis (Figure 1). Rubber products contain approximately
93-95% rubber and 3% protein. The make-up of the protein component
varies, depending on the source of the raw latex and the different
types of manufacturing processes used, and it is these different
polypeptides and proteins that cause IgE-mediated allergic
reactions. 90% of latex is strained, diluted with water, treated
with acid to coagulate the rubber particles and then pressed
into sheets on “calendering” machines. Most of this rubber
is used to make tyres. The remaining 10% is ammoniated to
prevent coagulation of the rubber particles and bacterial
growth, centrifuged to concentrate the rubber, treated with
preservatives and accelerators and “vulcanised” (heated with
sulphur to make it resistant to temperature changes). Rubber
produced in this way is used to make dipped products such
as gloves, condoms and balloons. It is the accelerators and
preservatives that are added to the latex to improve its physical
properties that cause T cell sensitisation and delayed hypersensitivity
reactions.
Prevalence
The prevalence of type I latex allergy in the general population
is less than 1%1, but in individuals
with a high degree of exposure, such as health care workers,
patients with spina bifida or congenital urogenital abnormalities
and rubber industry workers, the prevalence is much higher.
Prevalence rates in health care workers vary from 3-17%2,3
and up to 65% of children with spina bifida are sensitised4.
Additional risk factors for sensitisation are an atopic background1
and a history of hand dermatitis5,
with disruption of the skin barrier predisposing to sensitisation.
Many studies have found a higher prevalence of latex allergy
in women than men, but this may be because women are more
likely to be exposed to latex.
Type I Hypersensitivity
Allergens
Although more than 200 different polypeptides have been identified
in natural rubber latex, only a few of these are important
allergens. Characterisation by protein chemistry and/or molecular
cloning has shown that, in adults6,7,
prohevein (Hev b 6.01), hevein (Hev b 6.02), rubber elongation
factor/REF (Hev b 1) and acidic protein (Hev b 5) are major
allergens; while in children,8
REF (Hev b 1) and REF homologue (Hev b 3) are the major allergens.
The antigen content of manufactured goods varies greatly,
depending mainly on the manufacturing processes used, but
also on the natural variations in protein content that occur
in latex. Allergen content in different brands of latex gloves,
for example, has been found to vary 3,000 fold. If gloves
are powdered with cornstarch, as a donning lubricant, inhalation
of latex proteins is possible, since the latex proteins are
able bind to the cornstarch particles which are easily aerosolised
and may remain airborne for hours. The particles are small
(1-3µ in diameter) and may be inhaled. Measurement of
latex allergen concentration in air samples from a large medical
centre showed that in some sites where powdered gloves were
frequently used there was over 600 times more latex protein
in the air than at sites where powdered gloves were seldom/never
used9 (Figure 2).
Symptoms
Urticaria, angioedema, rhinitis, conjunctivitis, asthma and
anaphylaxis may occur as a result of type I, IgE-mediated
hypersensitivity to latex proteins. 80% of reported reactions
are due to rubber gloves or urinary catheters, with contact
urticaria being the most common symptom. Anaphylaxis has usually
occurred per-operatively or during barium-enema examinations
and the onset of symptoms is usually between 15 – 120 minutes
post-procedure. A small number of patients have died due to
latex-induced anaphylaxis10.
Latex – Food Cross-Reactivity
Approximately 50% of individuals who are latex-allergic are
also allergic to various foods. In particular, they may be
allergic to different fruits11,
hence the “Latex-Fruit” Syndrome. The cross-reactivity is
thought to occur because of specific IgE which recognises
antigenic epitopes on proteins which are structurally similar
in latex and other plants. For example, specific IgE against
hevein and hevamine has been shown to cross-react with other
plant proteins using techniques such as RAST-inhibition and
immunoblotting inhibition assays. The most frequent cross-reactivity
occurs with avocado, banana, chestnut and kiwi, but there
are many other foods which may also cross-react, including
celery, fig, grapefruit, mango, melon, papaya, passion fruit,
pear, peaches, pineapple, potato, soybean, stone fruits (apricot,
nectarine, peach, plum), and tomatoes. It is important to
discuss possible food-related symptoms in individuals with
latex allergy, but also remember that sIgE to various cross-reacting
foods may be found without the person having clinical symptoms
on exposure to that particular food (Figure 3).
Type IV Hypersensitivity
Type IV or delayed hypersensitivity causes allergic contact
dermatitis, often referred to as “rubber glove eczema”. It
occurs when T cells become sensitised to rubber additives
(accelerators) that are added to the rubber during manufacturing
to improve the physical qualities of the finished products.
The main additives are thiurams, carbamates and mercaptobenzothiazole
(MBT). Workers in the adhesives and clothing industries, as
well as health care workers and rubber industry workers are
particularly at risk. The acute phase of the reaction occurs
48-96 hours after exposure, with vesicular lesions on the
back of the hands. Chronic exposure leads to skin thickening
(acanthosis) and characteristic eczematous changes. It should
be remembered that non-allergic irritant skin rashes due to
rubber gloves are more common than eczematous or urticarial
rashes.
Diagnosis
Type I latex allergy is diagnosed on the basis of clinical
history and detection of sIgE either in vivo or in
vitro.12
A clinical questionnaire helps to identify “at risk” groups,
such as health care workers or patients with spina bifida,
an atopic background, presence of hand dermatitis, latex exposure
either at work or per-operatively, food allergies and previous
Type I and Type IV allergic reactions to latex.
Skin prick testing (SPT) for sIgE to latex is the most reliable
diagnostic method, with sensitivity and specificity rates
of almost 100% being reported in some series13.
One standardised SPT allergen preparation (Stallergenes, S.A.,
Fresnes, France) and several non-standardised preparations
are available. It is also possible to SPT through latex gloves,
or to soak pre-weighed samples of gloves in saline for 1-2
hours at 37° to produce a SPT reagent, or use ammoniated
or non-ammoniated latex to prepare SPT reagents. Care must
be taken if gloves are used as the allergen source, because
of the great variability in their allergen content; anaphylaxis
has been reported following SPT. Intradermal testing is much
more sensitive, but carries a correspondingly greater risk
of anaphylaxis.
Several commercial assays are available to detect sIgE in
vitro e.g. AlaSTAT (DPC) and ImmunoCAP (Pharmacia). The
sensitivity and specificity of these systems is variable and
may depend on natural variations in the allergen content of
the source material, cross-reactivity with other sIgE ( e.g.
food-specific IgE), the population being studied (e.g. spina
bifida patients may have very high sIgE levels, whilst levels
tend to be lower in health care workers) and threshold limits
of the different assays. The presence of sIgE does not always
mean that the individual will have clinical symptoms as sIgE
may be present for months or years before clinical problems
occur.
Other methods used to diagnose latex allergy include immunoblotting
techniques, basophil histamine release (which, although highly
sensitive, requires fresh cells and is difficult to standardise)
and provocation testing. Provocation techniques include “glove
use” methods, where the appearance of urticarial lesions constitutes
a positive result, and inhalational challenges with nebulised
aqueous extracts of latex or by exposure to cornstarch particles
with adsorbed latex proteins, where reductions in peak flow
and FEV1 are measured. Provocation testing is potentially
dangerous and resuscitation facilities should be available.
Diagnosis of type IV hypersensitivity is by patch testing
to rubber or rubber additives, which, by convention, is performed
in Dermatology clinics.
Manufacturing issues
It is possible to reduce the protein content of latex products
by manufacturing techniques such as double-centrifugation,
improved washing, steam sterilization, chlorination and enzyme
digestion. The Modified Lowry Assay is now recommended as
the standard technique for detecting extractable proteins
in natural rubber latex gloves. Unfortunately, rubber additives
may interfere with the assay and the technique measures total
protein rather than allergenic protein, but nevertheless
the total protein concentration correlates quite well with
SPT results14. The term “hypo-allergenic”
is no longer recommended since allergen content per se is
not measured.
Natural rubbers are available from other plants, for example
the guayule bush (Parthenium argentatum), a desert
shrub that grows in S.W. USA which has large quantities of
natural rubber in its bark. The extraction techniques needed
to harvest the rubber result in a low protein content, suggesting
that guayule rubber would be less likely to cause type I hypersensitivity
reactions. Guayule rubber products are not yet commercially
available. Synthetic rubbers and plastics can be used in place
of natural latex and many different brands of glove made from
these materials are available. Unfortunately, these materials
may be more expensive than natural latex and the gloves do
not always provide such good protection, strength and elasticity.
Prevention
Primary prevention aims to prevent latex sensitisation, by
avoiding latex exposure15.
This may be difficult as latex is very widely used (Table
1) and latex-containing products are not always labelled.
In addition, latex proteins may be transferred via gloves
or hands and may be found in the atmosphere adsorbed to cornstarch
particles.
| Adhesive tape |
Ambu bags |
| Aprons |
Balloons |
| Bandages (elastic and compression) |
Blood pressure cuffs |
| Catheters |
Condoms |
| Drains (surgical) |
Dummies |
| Electrode pads |
Endotracheal tubes |
| Eye shields |
Gloves |
| Haemodialysis equipment |
Handgrips |
| Head straps |
Hot water bottles |
| Intravenous equipment (injection
ports) |
Masks |
| Mattresses |
Plasters |
| Pressure stockings |
Protective sheets |
| Raincoats |
Rubber toys |
| Shoes |
Shower and swimming hats |
| Stethoscope tubing |
Stoppers |
| Stretch textiles |
Syringe plungers |
| Tourniquets |
Tyres |
| Underwear |
Ventilator tubes |
|
| Table 1. Medical
and Non-Medical Products that may contain Latex |
High risk groups should be identified and offered testing
for latex allergy and advice on latex avoidance, the possibility
of food cross-reactions and patient support groups. All procedures
on patients with a positive history of latex allergy should
be conducted in a latex-free environment and, if possible,
patients with spina bifida should avoid exposure to latex
from birth. Individuals at high risk of sensitisation should
use powder-free, low protein gloves, or preferably gloves
made from alternative materials.
Secondary prevention aims to prevent exposure in sensitised
individuals. As most reactions to medical devices in sensitised
patients are due to gloves or bladder catheters, non-latex
gloves and catheters should always be used. Operations should
be conducted in a latex-free environment and, as a precaution,
pre-medication with steroids and antihistamines is sometimes
advised to try and reduce the severity of an anaphylactic
reaction should there be inadvertent exposure to latex. Most
hospitals now have specific policy documents on latex allergy.
Those with a history of anaphylaxis should wear an allergy
bracelet and carry latex-free gloves.
Although there have been preliminary reports on latex desensitisation,
immunotherapy is not yet routinely available.
|